Chromatography is a separation method based on the distribution difference of compounds of a mixture between a mobile phase and a stationary phase, also called an adsorbent phase. The compounds are separated by percolating a liquid, gas or supercritical solvent in a device (a column) filled with an adsorbent phase. This method is widely applied as an analysis technique in order to identify and quantify the compounds of a mixture. It may also be applied as a purification technique.
Depending on the needs, different chromatography methods are used for achieving purification of molecules. These methods may be classified according to several criteria: the method may be discontinuous or continuous; the systems may include one or more columns; the composition of the eluent may be isocratic or a gradient may be effected.
Elution chromatography or batch chromatography is widely used. This method is based on discontinuous injection of the mixture to be purified in a column filled with the suitable stationary phase which is percolated with an eluent ensuring migration and separation of the products in the column. The separated products are drawn off at the column outlet. The injections may be repeated periodically with a period time allowing the separation to be retained between successive injections.
So-called batch chromatography is a widespread method, notably at a small and medium scale. It is a simple method to apply (a single column) which proves to be generally efficient, but not very performing in terms of productivity. The latter is generally low and the purified products are generally highly diluted in the elution solvent.
The idea of producing a counter-current between the eluting phase and the adsorbing phase was explored in order to give rise to the concept of a True Moving Bed. In 1961, a method appeared, the “Simulating Moving Bed”, (SMB), with which the movement of the solid may be simulated by a clever connection between the columns. It is characterized in that the points for introducing the feed and eluent are advanced periodically in the direction of flow of the main fluid, while the points for drawing off a raffinate and an extract are advanced simultaneously and according to a same increment.
Document EP-A-1 716 900 describes the integration of a method with a driving-force gradient into an SMB method. The document describes a method for continuous or quasi-continuous purification of a mixture containing several compounds. As in SMB, several areas are applied. The purification is accomplished by means of at lest two, preferably three individual chromatography columns into which the mixture is introduced, by means of a solvent. The mixture containing several compounds comprises at least lightweight impurities, an intermediate product to be purified and heavy impurities. The columns are used according to at least one step or one position in a batch mode. In this mode, the outlet of a column is used for drawing off the intermediate product. Columns are also used in at least one step or one position in a continuous or quasi-continuous mode. In this mode, the outlet of at least one column is in fluid connection connected to the inlet of at least one other column. The batch mode and the continuous or quasi-continuous modes are carried out synchronously or sequentially. After or in a switching period, the columns are moved in a direction opposite to the general direction of the solvent flow.
A drawback of this method is that it requires a complex device for applying it and simulation tools for understanding it.